Prognostic Value of Global Coronary Flow Reserve Before and After Elective Percutaneous Coronary Intervention in Patients with Chronic Coronary Syndrome.

BACKGROUND: Impaired global coronary flow reserve (G-CFR), evaluated through phase-contrast cine cardiovascular magnetic resonance (PC-CMR), has been linked to worse outcomes in patients with cardiovascular disease. This study aimed to investigate the prognostic value of G-CFR improvement, as evaluated using PC-CMR imaging pre- and post-percutaneous coronary intervention (PCI). METHODS: In this single-center study, 320 patients with chronic coronary syndrome (CCS) who underwent pre- and post-PCI PC-CMR measurements were followed-up to determine major adverse cardiac or cerebrovascular events (MACCE) predictors. MACCE was defined as a composite of cardiac death, nonfatal myocardial infarction, hospitalization due to heart failure, or ischemic stroke. The association between CMR parameters, including baseline data, G-CFR changes post-PCI and MACCE was investigated. RESULTS: G-CFR improvement was observed in 165 (51.6%) patients, while MACCE occurred in 26 (8.1%) during a median follow-up period of 2.5 years. G-CFR improvement was significantly associated with a lower pre-PCI G-CFR. The log-rank test revealed a significant association between patients without G-CFR improvement post-PCI and a poor prognosis. Patients with lower pre-PCI G-CFR and lack of G-CFR improvement exhibited the highest incidence of MACCE. The multivariable Cox proportional hazard model revealed that lack of G-CFR improvement was an independently significant MACCE predictor from pre-PCI G-CFR and SYNTAX score. CONCLUSIONS: Besides the association between pre- and post-PCI lower G-CFR and worse prognosis, the presence or absence of G-CFR improvement post-PCI may provide novel insights into the prognosis following elective PCI in patients with CCS.

Association of Coronary Computed Tomography-Defined Myocardial Bridge With Pre- and Post-Procedural Fractional Flow Reserve in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Myocardial bridge (MB) is a common coronary anomaly characterized by a tunneled course through the myocardium. Coronary computed tomography angiography (CCTA) can identify MB. The impact of MB detected by CCTA on coronary physiological parameters before and after percutaneous coronary intervention (PCI) is unknown. METHODS AND RESULTS: We investigated 141 consecutive patients who underwent pre-PCI CCTA and fractional flow reserve (FFR)-guided elective PCI for de novo single proximal lesions in the left anterior descending artery (LAD). We compared clinical demographics and physiological parameters between patients with and without CCTA-defined MB. MB was identified in 46 (32.6%) patients using pre-PCI CCTA. The prevalence of diabetes was higher among patients with MB. Median post-PCI FFR values were significantly lower among patients with than without MB (0.82 [interquartile range 0.79-0.85] vs. 0.85 [interquartile range 0.82-0.89]; P=0.003), whereas pre-PCI FFR values were similar between the 2 groups. Multivariable linear regression analysis revealed that the presence of MB and greater left ventricular mass volume in the LAD territory were independently associated with lower post-PCI FFR values. Multivariable logistic regression analysis also revealed that the presence of MB and lower pre-PCI FFR values were independent predictors of post-PCI FFR values ≤0.80. CONCLUSIONS: CCTA-defined MB independently predicted both lower post-PCI FFR as a continuous variable and ischemic FFR as a categorical variable in patients undergoing elective PCI for LAD.

Predictors of Optical Coherence Tomography-Defined Calcified Nodules in Patients With Acute Coronary Syndrome　- A Substudy From the TACTICS Registry.

BACKGROUND: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry. METHODS AND RESULTS: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN. CONCLUSIONS: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Detection of unrecognized myocardial infarction by preprocedural transthoracic echocardiography in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Previous studies showed that unrecognized myocardial infarction (UMI) identified on cardiac magnetic resonance (CMR) was related to worse prognosis. We aimed to investigate the efficacy of preprocedural transthoracic echocardiography (TTE) to detect the presence of UMI in patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 138 patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF) without history of myocardial infarction or revascularization were retrospectively studied. UMI was evaluated with pre-PCI late gadolinium enhancement (LGE)-CMR. TTE and two-dimensional speckle-tracking echocardiography (2D-STE) were performed before PCI. All patients were divided into two groups according to the presence or absence of UMI, and clinical and echocardiographic findings were compared between these two groups. RESULTS: UMI was detected in 43 patients (31.2%). Multivariable logistic regression analysis revealed that higher SYNTAX score, the presence of wall motion abnormalities (WMAs) and lower global longitudinal strain (GLS) were independent predictors of the presence of UMI. Furthermore, GLS provided incremental efficacy for the detection of UMI over abnormal Q waves, SYNTAX score and WMAs. CONCLUSIONS: Preprocedural TTE in combination with 2D-STE could help identify patients with UMI regardless of the presence or absence of ECG findings and WMAs.

Prognostic Implications of Fractional Flow Reserve and Coronary Flow Reserve After Drug-Eluting Stent Implantation.

BACKGROUND: Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) provides prognostic information, but limited data are available regarding prognostication using post-PCI coronary flow reserve (CFR). In this study we aimed to assess the prognostic value of post-procedural FFR and CFR for target vessel failure (TVF) after PCI.Methods and Results: This lesion-based post-hoc pooled analysis of previously published registry data involved 466 patients with chronic coronary syndrome with single-vessel disease who underwent pre- and post-PCI FFR and CFR measurements, and were followed-up to determine the predictors of TVF. The prognostic value of post-PCI CFR and FFR was compared with that of FFR or CFR alone. Post-PCI FFR/CFR discordant results were observed in 42.5%, and 10.3% of patients had documented TVF. Receiver-operating characteristic curve analysis revealed that the optimal cutoff values of post-PCI FFR and CFR to predict the occurrence of TVF were 0.85 and 2.26, respectively. Significant differences in TVF were detected according to post-PCI FFR (≤0.85 vs. >0.85, P=0.007) and post-PCI CFR (<2.26 vs. ≥2.26, P<0.001). Post-PCI FFR ≤0.85 and post-PCI CFR <2.26 were independent prognostic predictors. CONCLUSIONS: After PCI completion, discordant results between FFR and CFR were not uncommon. Post-PCI CFR categorization showed incremental prognostic value for predicting TVF independent of post-PCI FFR risk stratification.

Effect of percutaneous coronary intervention on global hemodynamics and the prevalence of residual microvascular dysfunction.

OBJECTIVES: We aimed to examine the changes in hyperemic coronary sinus flow (CSF) and global coronary flow reserve (g-CFR) after percutaneous coronary intervention (PCI) and investigate the predictors to improve these metrics and the prevalence of residual coronary microvascular dysfunction (CMD). METHODS: This prospective, single-center study included 118 patients with stable coronary artery disease undergoing PCI for a single proximal lesion. Phase-contrast cine-cardiac magnetic resonance (PC-CMR) was used to assess hyperemic CSF (HCSF) and g-CFR, before and after PCI. Residual CMD was defined as concordantly impaired post-PCI HCSF (<2.3 ml/min/g) and g-CFR (<2.0). RESULTS: HCSF significantly increased, although 38 (32.2%) patients showed a decrease. There was no significant change in g-CFR despite fractional flow reserve (FFR) improvement in all target territories. Concordantly increased HCSF and g-CFR were effectively discriminated by adding PC-CMR-derived information to pre-PCI FFR. Residual CMD was observed in 30 (25.4%) patients and was associated with pre-PCI renal dysfunction and lower pre-PCI rest and hyperemic CSF, but not with pre-PCI regional physiological indices. CONCLUSIONS: FFR-guided PCI was associated with increased HCSF, but not with increased g-CFR. After uncomplicated PCI, one-quarter of patients showed residual CMD. Our approach may help identify patients who may benefit from increased coronary perfusion or show residual CMD.

Characteristic findings of microvascular dysfunction on coronary computed tomography angiography in patients with intermediate coronary stenosis.

OBJECTIVES: We aimed to assess the prevalence of coexistence of coronary microvascular dysfunction (CMD) in patients with intermediate epicardial stenosis and to explore coronary computed tomography angiography (CCTA)-derived lesion-, vessel-, and cardiac fat-related characteristic findings associated with CMD. METHODS: A retrospective cross-sectional single-center study included a total of 177 patients with intermediate stenosis in the left anterior descending artery (LAD) who underwent CCTA and invasive physiological measurements. The 320-slice CCTA analysis included qualitative and quantitative assessments of plaque, vessel, epicardial fat volume (ECFV) and epicardial fat attenuation (ECFA), and pericoronary fat attenuation (FAI). CMD was defined by the index of microcirculatory resistance (IMR) ≥ 25. RESULTS: In the entire cohort, median fractional flow reserve (FFR) and median IMR values were 0.77 (0.69-0.84) and 19.0 (13.7-27.7), respectively. The prevalence of CMD was 32.8 % (58/177) in the total cohort. The coexistence of CMD and functionally significant stenosis was 34.3 % (37/108), whereas CMD in nonsignificant intermediate stenosis was 30.4 % (21/69). CMD was significantly associated with greater lumen volume (p = 0.031), greater fibrofatty and necrotic component (FFNC) volume (p = 0.030), and greater ECFV (p = 0.030), but not with FAI (p = 0.832) and ECFA (p = 0.445). On multivariable logistic regression analysis, vessel volume, vessel lumen volume, lesion remodeling index, ECFV, and lesion FFNC volume were independent predictors of CMD. CONCLUSIONS: The prevalence of CMD was about one-third in patients with intermediate stenosis in LAD regardless of the presence or absence of functional stenosis significance. The integrated CCTA assessment may help in the identification of CMD. KEY POINTS: • The coexistence of coronary microvascular dysfunction (CMD) and functionally significant stenosis was 34.3 %, whereas CMD in nonsignificant intermediate stenosis was 30.4 %. • Coronary computed tomography angiography (CCTA)-derived CMD characteristics were vessel volume, vessel lumen volume, remodeling index, epicardial fat volume, and fibrofatty necrotic core volume. • Integrated CCTA assessment may help identify the coexistence of CMD and epicardial stenosis.

Clinical Significance of Increased Computed Tomography Attenuation of Periaortic Adipose Tissue in Patients With Abdominal Aortic Aneurysms.

BACKGROUND: Recent imaging studies reported an association between vascular inflammation and progression of abdominal aortic aneurysm (AAA). This study investigated the clinical significance of periaortic adipose tissue inflammation derived from multidetector computed tomography angiography (MDCTA).Methods and Results:Patients with asymptomatic AAA (n=77) who underwent an index and >6 months follow-up MDCTA examinations were retrospectively investigated. MDCTA analysis included AAA diameter and the periaortic adipose tissue attenuation index (PAAI). The PAAI was defined as the mean CT attenuation value within a predefined range from -190 to -30 Hounsfield units of adipose tissue surrounding the AAA. The growth rate of the AAA was calculated as the change in diameter. AAA progression (AP) was defined as an AAA growth rate ≥5 mm/year. Univariate and multivariate logistic regression analysis were performed to determine the predictors of AP. AP was observed in 19 patients (24.7%), the median baseline AAA diameter was 38.9 mm (interquartile range [IQR] 32.7-42.9 mm), and the median growth rate was 3.1 mm/year (IQR 1.5-4.9 mm/year). Baseline AAA diameter (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.05-1.28; P=0.001) and PAAI (OR 1.12; 95% CI 1.05-1.20; P=0.004) were independent predictors of AP. CONCLUSIONS: PAAI was an independent and significant predictor of AP, supporting the notion that local adipose tissue inflammation may contribute to aortic remodeling.

Impact of pericoronary adipose tissue inflammation on left ventricular hypertrophy and regional physiological indices in stable coronary artery disease patients with preserved systolic function.

Systemic low-grade inflammation has been shown to be associated with left ventricular hypertrophy (LVH). However, the relationship between pericoronary adipose tissue attenuation (PCATA) and both LVH and regional physiological indices remains unknown. This study aimed to evaluate the association of PCATA with LVH and regional physiological indices in stable coronary artery disease (CAD) patients with preserved systolic function. A total of 114 CAD patients who underwent coronary CT angiography (CTA) and invasive physiological tests showing ischemia due to a single de novo lesion were included in the study. On proximal 40-mm segments of all three major coronary vessels on CTA, PCATA was assessed by the crude analysis of the mean CT attenuation value [- 190 to - 30 Hounsfield units [HU)] and the culprit vessel PCATA was used for the analysis. Regional physiological indices were invasively obtained by pressure-temperature sensor-tipped wire. The patients were divided into three groups by culprit vessel PCATA tertiles, and clinical, CTA-derived, and physiological indices were compared. Univariable and multivariable analyses were further performed to determine the predictors of LVH. Angiographic stenosis severity, culprit lesion locations, culprit vessel fractional flow reserve, coronary flow reserve, index of microcirculatory resistance, total and target vessel coronary calcium score, and biomarkers including high-sensitivity C-reactive protein were not different among the groups. The left ventricular (LV) mass, LV mass index (LVMI), and LV mass at risk were all significantly different in the three groups with the greatest values in the highest tertile group (all, P < 0.05). On multivariable analysis, male gender, NT-proBNP, and PCATA were independent predictors of LVMI. Culprit vessel PCATA was significantly associated with LVMI, but not with regional physiology in CAD patients with functionally significant lesions and preserved systolic function. Our results may offer insight into the pathophysiological mechanisms linking pericoronary inflammation and LVH to worse prognosis.

All Resting Physiological Indices May Not Be Equivalent　- Comparison Between the Diastolic Pressure Ratio and Resting Full-Cycle Ratio.

BACKGROUND: Differences between resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have not been sufficiently discussed. This study aimed to investigate if there is a difference in diagnostic performance between RFR and dPR for the functional lesion assessment and to assess if there are specific characteristics for discordant revascularization decision-makings between RFR and dPR.Methods and Results:A total of 936 intermediate lesions in 776 patients who underwent measurements of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) were retrospectively studied. Physiological indices were measured from anonymized pressure recordings at an independent core laboratory. Both RFR and dPR measures were highly correlated (r=0.997, P<0.001), with equivalent diagnostic performance relative to FFR-based decision-makings measured by using a dichotomous threshold of 0.80 (accuracy, 79.7% vs. 80.1%, respectively, P=0.960). The rate of diagnostic discordance was 4.7% (44/936), with no RFR-/dPR+ lesions observed. An overall significant difference in FFR and CFR values were detected among RFR/dPR-based classifications. The prevalence of positive studies was significantly higher for RFR than dPR (54.3% vs. 49.6%, respectively, P=0.047) when using the cut-off value of 0.89. CONCLUSIONS: Both RFR and dPR were highly correlated, but the prevalence of positive studies was significantly different. The revascularization rate may differ significantly according to the resting index used.

Ventricular Fibrillation During Optical Coherence Tomography/Optical Frequency Domain Imaging　- A Large Single-Center Experience.

BACKGROUND: The risks of ventricular fibrillation (Vfib) associated with frequency-domain optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) remain undetermined.Methods and Results:We retrospectively studied the occurrence of Vfib during OCT/OFDI for unselected indications. The frequency of Vfib and patient and procedural characteristics were investigated. A total of 4,467 OCT/OFDI pullback examinations were performed in 1,754 patients (median of 2.0 [2.0-3.0] pullbacks for 1.0 [1.0-1.3] vessels). OCT/OFDI was performed during PCI in 899 patients (51.3%). The contrast injection volume per pullback was 14.4 (11.7-17.2) mL with a flow rate of 3.4 (3.2-3.5) mL/s. Vfib occurred in 31 pullbacks (0.69%) in 30 patients (1.7%). No cases of Vfib occurred when using low-molecular-weight dextran. On multivariate analysis, contrast volume was the only independent factor for predicting Vfib (odds ratio, 1.080; 95% confidence interval, 1.008-1.158, P=0.029). The best cutoff value of contrast volume for predicting Vfib was 19.2 mL (area under the curve, 0.713, P<0.001; diagnostic accuracy, 87.1%). CONCLUSIONS: The present large, single-center registry study indicated that Vfib during OCT/OFDI was rare for unselected indications. Contrast injection volume used to displace blood should be limited to avoid Vfib.

IL-10-mediated signals act as a switch for lymphoproliferation in Human T-cell leukemia virus type-1 infection by activating the STAT3 and IRF4 pathways.

Human T-cell leukemia virus type-1 (HTLV-1) causes two distinct diseases, adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since there are no disease-specific differences among HTLV-1 strains, the etiological mechanisms separating these respective lymphoproliferative and inflammatory diseases are not well understood. In this study, by using IL-2-dependent HTLV-1-infected T-cell lines (ILTs) established from patients with ATL and HAM/TSP, we demonstrate that the anti-inflammatory cytokine IL-10 and its downstream signals potentially act as a switch for proliferation in HTLV-1-infected cells. Among six ILTs used, ILTs derived from all three ATL patients grew much faster than those from three HAM/TSP patients. Although most of the ILTs tested produced IFN-γ and IL-6, the production of IL-10 was preferentially observed in the rapid-growing ILTs. Interestingly, treatment with exogenous IL-10 markedly enhanced proliferation of the slow-growing HAM/TSP-derived ILTs. The IL-10-mediated proliferation of these ILTs was associated with phosphorylation of STAT3 and induction of survivin and IRF4, all of which are characteristics of ATL cells. Knockdown of STAT3 reduced expression of IL-10, implying a positive-feedback regulation between STAT3 and IL-10. STAT3 knockdown also reduced survivin and IRF4 in the IL-10- producing or IL-10- treated ILTs. IRF4 knockdown further suppressed survivin expression and the cell growth in these ILTs. These findings indicate that the IL-10-mediated signals promote cell proliferation in HTLV-1-infected cells through the STAT3 and IRF4 pathways. Our results imply that, although HTLV-1 infection alone may not be sufficient for cell proliferation, IL-10 and its signaling pathways within the infected cell itself and/or its surrounding microenvironment may play a critical role in pushing HTLV-1-infected cells towards proliferation at the early stages of HTLV-1 leukemogenesis. This study provides useful information for understanding of disease mechanisms and disease-prophylactic strategies in HTLV-1 infection.

Prognostic Value of Integrated Assessment of Cardiac Magnetic Resonance-Derived Global Coronary Flow Reserve and Cardiopulmonary Exercise Testing-Derived Peak Oxygen Consumption in Patients With Acute Myocardial Infarction.

Background: This study investigated the prognostic value of cardiovascular magnetic resonance (CMR)-derived global coronary flow reserve (G-CFR) in addition to cardiopulmonary exercise testing (CPET) variables in patients with acute myocardial infarction (AMI). Methods and Results: We investigated 127 patients with AMI who underwent primary or urgent percutaneous coronary intervention (PCI) and post-intervention CMR and CPET. The incidence of major cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent non-fatal myocardial infarction, re-hospitalization due to congestive heart failure, and stroke, was evaluated (median follow-up, 2.8 years). Patients with MACCE (n=14) had lower ejection fraction (EF) (50 [43-59] vs. 58 [51-63]%; P=0.014), lower G-CFR (1.74 [1.19-2.20] vs. 2.40 [1.61-3.66]; P=0.008), and lower peak oxygen consumption (V̇O2) (15.16±2.64 vs. 17.19±3.70 mL/kg/min; P=0.049) than patients without MACCE. G-CFR<2.33 and peak V̇O2 <15.65 mL/kg/min (cut-off values derived from receiver operating characteristic curve analyses) were significantly associated with the incidence of MACCE (log-rank test, P=0.01). The combination of low G-CFR and low peak V̇O2 improved risk discrimination for MACCE when added to the reference clinical model including age, male sex, post-PCI peak creatine kinase, EF, and left anterior descending artery culprit lesion. Conclusions: G-CFR and peak V̇O2 showed incremental prognostic information compared with the reference model using historically important clinical risk factors, indicating that this approach may help identify high-risk patients who suffer subsequent adverse events.

Association between optical coherence tomography-defined culprit morphologies and changes in hyperemic coronary flow after elective stenting assessed by transthoracic Doppler echocardiography.

BACKGROUND: Stress-transthoracic Doppler echocardiography (S-TDE) provides a noninvasive assessment of coronary flow parameters in the left anterior descending artery (LAD). However, the association between morphological characteristics and coronary flow changes after elective percutaneous coronary intervention (PCI) remains unclear. We aimed to evaluate the relationships between periprocedural coronary flow changes observed on S-TDE and lesion-specific plaque characteristics obtained by optical coherence tomography (OCT) in the interrogated vessels in patients with chronic coronary syndrome (CCS). METHODS AND RESULTS: Patients with CCS who underwent pre- and post-PCI S-TDE and elective fractional flow reserve (FFR)-guided PCI under OCT guidance for de novo single LAD lesions were included. S-TDE-derived hyperemic diastolic peak flow velocity (hDPV) was used as a surrogate for coronary flow. Lesions were categorized into two groups based on the %hDPV increase or decrease. The baseline clinical, physiological, and OCT findings were compared between the groups. In total, 103 LAD lesions were studied in 103 patients. After PCI, hDPV significantly increased from 55.6 cm/s to 69.5 cm/s (P<0.01), with a median %hDPV increase of 27.2 (6.32-59.1) %, while %hDPV decreased in 20 (19.4%) patients. The FFR improved in all patients. On OCT, layered plaques were more frequently present in the culprit vessels in the %hDPV-decrease group than in the %hDPV-increase group (85.0% vs. 50.6%, P = 0.01). Multivariable logistic regression analysis showed that the presence of layered plaques and high pre-PCI hDPV were independent predictors of %hDPV decrease. CONCLUSIONS: In patients who underwent successful uncomplicated elective PCI for de novo single LAD lesions, the presence of layered plaques was independently associated with hyperemic coronary flow decrease as assessed by S-TDE.

Predictors and prognostic value of coronary computed tomography angiography for unrecognized myocardial infarction in patients with chronic coronary syndrome.

OBJECTIVE: Unrecognized myocardial infarction (UMI) on delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) and coronary computed tomography angiography (CCTA) derived high-risk features provide prognostic information in patients with chronic coronary syndrome (CCS). The study aimed to assess the prognostic value of UMI and predictors of UMI using CCTA in patients with CCS who underwent elective percutaneous coronary intervention (PCI). METHODS: This study enrolled 181 patients with CCS who underwent DE-CMR and CCTA before elective PCI. The CCTA-derived predictors of UMI and the association of baseline clinical characteristics, CCTA findings, and CMR-derived factors, including UMI, with MACEs, defined as death, nonfatal myocardial infarction, unplanned late revascularization, hospitalization for congestive heart failure, and stroke, were investigated. RESULTS: UMI was detected in 57 (31.5%) patients. ROC analysis revealed that the optimal cut-off values of Agatston score and mean peri-coronary fat attenuation index (FAI) for predicting the presence of UMI were 397 and -69.8, respectively. The multivariable logistic regression analysis revealed that left ventricular mass, Agatston score >397, mean FAI >-69.8, positive remodeling of the target lesion, and CCTA-derived stenosis severity were independent predictors of UMI. Kaplan-Meier analysis revealed that patients with UMI were associated with increased risk of MACEs. The Cox proportional hazards analysis showed post-PCI minimum lumen diameter and the presence of UMI were independent predictors of MACEs. The risk of MACEs significantly increased according to the number of four preprocedural CCTA-relevant features of UMI. CONCLUSION: Preprocedural comprehensive CCTA analysis may help predict the presence of UMI and provide prognostic information in patients with CCS who underwent PCI.

Noninvasive transthoracic doppler flow velocity and invasive thermodilution to assess coronary flow reserve.

Background: Coronary flow reserve (CFR) provides prognostication and coronary physiological information, including epicardial coronary stenosis and microvascular function. The relationship between stress transthoracic Doppler echocardiography (TDE)-derived coronary flow velocity reserve (CFRS-TDE) and thermodilution-derived coronary flow reserve (CFRthermo) before and after elective percutaneous coronary intervention (PCI) remains unclear. Methods: This single-center prospective registry study evaluated patients who underwent fractional flow reserve (FFR)-guided elective PCI for left anterior descending artery (LAD) lesions with wire-based invasive physiological measurements and pre- and post-PCI stress TDE examinations. Results: A total of 174 LAD lesions from 174 patients were included in the final analysis. A modest correlation was detected between the pre-PCI CFRS-TDE and the pre-PCI CFRthermo (r=0.383, P<0.001). The frequently used CFRS-TDE threshold of 2.0 corresponded to a pre-PCI CFRthermo of 2.18. Pre-PCI CFRS-TDE underestimated pre-PCI CFRthermo [1.89 (1.44-2.31) vs. 2.05 (1.38-2.93), P<0.001]. Both CFRS-TDE and CFRthermo increased significantly post-PCI [pre-PCI CFRS-TDE 1.89 vs. post-PCI CFRS-TDE 2.33, P<0.001; pre-PCI CFRthermo 2.05 (1.38-2.93) vs. post-PCI CFRthermo 2.59 (1.63-3.55), P<0.001]. In contrast, there was no significant relationship between changes in CFRS-TDE and changes in CFRthermo after PCI (r=0.008, P=0.915) or between post-PCI CFRS-TDE and post-PCI CFRthermo (r=0.054, P=0.482). Conclusions: Pre-PCI CFRS-TDE and CFRthermo are modestly correlated, but post-PCI CFRS-TDE and CFRthermo have no correlation. CFRS-TDE and CFRthermo are not interchangeable, particularly post-PCI, suggesting that the two metrics represent different coronary physiologies after PCI.

Combined Assessment of Fractional Flow Reserve and Coronary Flow Velocity Reserve after Drug-Eluting Stent Implantation.

BACKGROUND: Coronary flow velocity reserve (CFVR) can be measured noninvasively using stress transthoracic Doppler echocardiography (S-TDE). The prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to investigate the prognostic value of post-PCI CFVR and its additional efficacy to fractional flow reserve (FFR) in patients undergoing elective PCI. METHODS: A retrospective study was conducted involving 187 consecutive patients with chronic coronary syndrome who underwent elective PCI guided by FFR for the left anterior descending coronary artery. Pre- and post-PCI wire-based FFR and CFVR assessments of the left anterior descending coronary artery using S-TDE were performed in all patients. The association between post-PCI clinical and physiologic parameters and major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, heart failure, and unplanned remote target vessel revascularization, was evaluated. RESULTS: Three-quarters of patients exhibited CFVR increase after PCI, while all patients showed FFR improvement. During a median follow-up period of 1.5 years, MACE occurred in 21 patients (11.2%). Among clinical demographics, patients with MACE had higher levels of N-terminal pro-brain natriuretic peptide compared with those without MACE (median, 615 pg/mL [interquartile range, 245-1,500 pg/mL] vs 180 pg/mL [interquartile range, 70-559 pg/mL]; P = .010). Post-PCI S-TDE-derived CFVR was lower in patients with MACE, while post-PCI FFR showed a nonsignificant tendency to be lower in patients with MACE. In a multivariable analysis, higher NT-proBNP (adjusted hazard ratio, 1.33; 95% CI, 1.02-1.74; P = .038), post-PCI CFVR ≤ 2.0 (adjusted hazard ratio, 2.93; 95% CI, 1.16-7.40; P = .023), and post-PCI FFR ≤ 0.82 (adjusted hazard ratio, 3.93; 95% CI, 1.52-10.18; P = .005) were independently associated with MACE. CONCLUSIONS: In patients with chronic coronary syndrome who underwent successful elective PCI for left anterior descending coronary artery, the combined assessment of S-TDE-derived post-PCI CFVR and post-PCI FFR provided a significant association with the occurrence of MACE.

Multimodality coronary imaging to predict non-culprit territory unrecognized myocardial infarction in Non-ST-Elevation acute coronary syndrome.

PURPOSE: Unrecognized myocardial infarction (UMI) detected by cardiac magnetic resonance (CMR) imaging is associated with adverse outcomes in patients with acute and chronic coronary syndrome. This study aimed to assess the predictors of optical coherence tomography (OCT) and coronary computed tomography angiography (CCTA) findings for non-infarct-related (non-IR) territory UMI in patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: We investigated 69 patients with a first clinical episode of NSTE-ACS who underwent pre-percutaneous coronary intervention (PCI) 320-slice CCTA, uncomplicated urgent PCI with OCT assessment within 24 h of admission, and post-PCI CMR. UMI was assessed using late gadolinium enhancement to identify regions of hyperenhancement with an ischemic distribution pattern in non-IR territories. RESULTS: Non-IR UMI was detected in 11 patients (15.9%). Lower ejection fraction, higher Gensini score, higher Agatston score, high pericoronary adipose tissue attenuation (PCATA), OCT-defined culprit lesion plaque rupture, and OCT-defined culprit lesion cholesterol crystal were significantly associated with the presence of non-IR UMI. On dividing the total cohort was divided into five groups according to the numbers of two OCT-derived risk factors and two CCTA-derived risk factors, the frequency of non-IR UMI frequency significantly increased according to the number of these relevant risk features (p < 0.001). Patients with all of the non-IR UMI risk factors showed 50% prevalence of non-IR UMI, compared with 2.2% of patients with low risk factors (≤ 2). CONCLUSIONS: Integrated CCTA and culprit lesion OCT assessment may help identify the presence of non-IR UMI, potentially providing prognostic information in patients with first NSTE-ACS episode.

Prognostic utility of the pericoronary fat attenuation index in patients with takotsubo cardiomyopathy.

BACKGROUND: The etiology of takotsubo cardiomyopathy (TCM) remains poorly understood and no optimal management strategy has been established. Identification of features associated with poor outcomes may improve the prognosis of patients with TCM. We aimed to identify the predictors of poor prognosis in patients with TCM using coronary computed tomography angiography (CCTA). METHODS: We enrolled consecutive patients with TCM who underwent CCTA during the acute disease phase. The pericoronary fat attenuation index (FAI) of adipose tissue was obtained from CCTA images. Major adverse cardiac and cerebrovascular events (MACCE) were defined as all-cause death, non-fatal myocardial infarction, stroke, rehospitalization due to congestive heart failure, and TCM recurrence. The relationships between patient characteristics and CCTA findings were compared between patients with and without MACCE. RESULTS: A total of 52 patients were included (10 men [19.2%]; mean age, 71 years). After a median follow-up of 23 months, MACCE had developed in 10 patients (19.2%). There were significant differences in clinical characteristics [including the three-vessel mean FAI (FAI-mean)] between patients with and without MACCE. Univariate Cox regression analyses showed that FAI-mean â€‹≥ â€‹-68.94 Hounsfield units (cut-off value derived from receiver operating characteristic curve analysis) (hazard ratio [HR], 13.52; 95% confidence interval [CI], 1.705-107.2; p â€‹= â€‹0.014) and NT-proBNP (HR, 1.000; 95% CI, 1.000-1.000; p â€‹= â€‹0.022) were significant predictors of MACCE. FAI-mean â€‹≥ â€‹-68.94 HU was significantly associated with MACCE (chi-squared statistic â€‹= â€‹10.3, p â€‹= â€‹0.001). CONCLUSION: In patients with TCM, a higher FAI-mean was significantly associated with poorer outcomes independent of the conventional risk factors.

Microvascular resistance reserve in the presence of functionally significant epicardial stenosis and changes after revascularization.

In the presence of functionally significant epicardial lesions, microvascular resistance reserve (MRR) calculation needs incorporation of collateral flow. Coronary fractional flow reserve (FFRcor ) requiring coronary wedge pressure (Pw ), which is an essential part of the true MRR calculation, is reportedly estimated by myocardial FFR (FFRmyo ) not requiring Pw measurement. We sought to find an equation to calculate MRR without the need for Pw . Furthermore, we assessed changes in MRR after percutaneous coronary intervention (PCI). An equation to estimate FFRcor was developed from a cohort of 230 patients who underwent physiological measurements and PCI. Corrected MRR was calculated using this equation and compared with true MRR in 115 patients of the different set of the validation cohort. True MRR was calculated using FFRcor . FFRcor and FFRmyo showed a strong linear relationship (r2  = 0.86) and an equation was FFRcor  = 1.36 × FFRmyo - 0.34. This equation provided no significant difference between corrected MRR and true MRR in the validation cohort. Pre-PCI lower coronary flow reserve and higher index of microcirculatory resistance were independent predictors of pre-PCI decreased true MRR. True MRR significantly decreased after PCI. In conclusion, MRR can be accurately corrected using an equation for FFRcor estimation without Pw .